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Aliases for WNK4 Gene

Aliases for WNK4 Gene

  • WNK Lysine Deficient Protein Kinase 4 2 3
  • PRKWNK4 3 4 6
  • Protein Kinase Lysine-Deficient 4 3 4
  • Protein Kinase With No Lysine 4 3 4
  • EC 2.7.11.1 4 64
  • PHA2B 3 6
  • Serine/Threonine-Protein Kinase WNK4 3
  • Protein Kinase, Lysine Deficient 4 2
  • EC 2.7.11 64

External Ids for WNK4 Gene

Previous Symbols for WNK4 Gene

  • PRKWNK4

Summaries for WNK4 Gene

Entrez Gene Summary for WNK4 Gene

  • This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009]

GeneCards Summary for WNK4 Gene

WNK4 (WNK Lysine Deficient Protein Kinase 4) is a Protein Coding gene. Diseases associated with WNK4 include pseudohypoaldosteronism, type iib and pseudohypoaldosteronism. Among its related pathways are Diuretics Pathway, Pharmacodynamics and Ion channel transport. GO annotations related to this gene include protein serine/threonine kinase activity. An important paralog of this gene is NRBP1.

UniProtKB/Swiss-Prot for WNK4 Gene

  • Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L.

Gene Wiki entry for WNK4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for WNK4 Gene

Genomics for WNK4 Gene

Genomic Location for WNK4 Gene

Start:
42,780,614 bp from pter
End:
42,797,066 bp from pter
Size:
16,453 bases
Orientation:
Plus strand

Genomic View for WNK4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for WNK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for WNK4 Gene

Regulatory Elements for WNK4 Gene

Proteins for WNK4 Gene

  • Protein details for WNK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96J92-WNK4_HUMAN
    Recommended name:
    Serine/threonine-protein kinase WNK4
    Protein Accession:
    Q96J92
    Secondary Accessions:
    • B0LPI0
    • Q8N8X3
    • Q8N8Z2
    • Q96DT8
    • Q9BYS5

    Protein attributes for WNK4 Gene

    Size:
    1243 amino acids
    Molecular mass:
    134739 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity). Interacts with KLHL3.
    SequenceCaution:
    • Sequence=BAC04669.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAC48387.1; Type=Frameshift; Positions=4; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for WNK4 Gene

    Alternative splice isoforms for WNK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for WNK4 Gene

Proteomics data for WNK4 Gene at MOPED

Post-translational modifications for WNK4 Gene

  • Phosphorylated by WNK1 and WNK3.
  • Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation and increased expression of KCNJ1 at the cell surface. Ubiquitinated by the BCR(KLHL2) complex.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys157, Lys175, Lys186, Lys226, Lys241, Lys328, Lys387, Lys393, Lys450, Lys454, Lys1010, Lys1144, Lys1157, and Lys1158

Other Protein References for WNK4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for WNK4 Gene

Gene Families for WNK4 Gene

Protein Domains for WNK4 Gene

UniProtKB/Swiss-Prot:

WNK4_HUMAN
Domain:
  • Contains 1 protein kinase domain.:
    • Q96J92
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.:
    • Q96J92
genes like me logo Genes that share domains with WNK4: view

Function for WNK4 Gene

Molecular function for WNK4 Gene

UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes increased activity (By similarity).
UniProtKB/Swiss-Prot Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L.

Enzyme Numbers (IUBMB) for WNK4 Gene

Gene Ontology (GO) - Molecular Function for WNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity ISS --
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 17721439
GO:0005524 ATP binding ISS --
genes like me logo Genes that share ontologies with WNK4: view
genes like me logo Genes that share phenotypes with WNK4: view

Animal Models for WNK4 Gene

MGI Knock Outs for WNK4:

miRNA for WNK4 Gene

miRTarBase miRNAs that target WNK4

No data available for Transcription Factor Targeting and HOMER Transcription for WNK4 Gene

Localization for WNK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for WNK4 Gene

Cell junction, tight junction. Note=Present exclusively in intercellular junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical collecting duct. WNK4 is part of the tight junction complex (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for WNK4 Gene COMPARTMENTS Subcellular localization image for WNK4 gene
Compartment Confidence
nucleus 2
plasma membrane 2
cytosol 1
extracellular 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for WNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005923 bicellular tight junction ISS --
genes like me logo Genes that share ontologies with WNK4: view

Pathways for WNK4 Gene

genes like me logo Genes that share pathways with WNK4: view

Pathways by source for WNK4 Gene

1 GeneGo (Thomson Reuters Life Sciences Research) pathway for WNK4 Gene
1 Cell Signaling Technology pathway for WNK4 Gene

Gene Ontology (GO) - Biological Process for WNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation ISS --
GO:0006811 ion transport ISS --
GO:0006821 chloride transport IEA --
GO:0008104 protein localization IEA --
GO:0035556 intracellular signal transduction ISS --
genes like me logo Genes that share ontologies with WNK4: view

Compounds for WNK4 Gene

(4) HMDB Compounds for WNK4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Chlorine
  • Cl2
16887-00-6
Magnesium
  • Magnesium
7439-95-4

(9) Novoseek inferred chemical compound relationships for WNK4 Gene

Compound -log(P) Hits PubMed IDs
thiazide 71 2
lysine 68.9 13
nacl 59.7 16
threonine 58 3
potassium 55.8 12
genes like me logo Genes that share compounds with WNK4: view

Transcripts for WNK4 Gene

Unigene Clusters for WNK4 Gene

WNK lysine deficient protein kinase 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for WNK4 Gene

No ASD Table

Relevant External Links for WNK4 Gene

GeneLoc Exon Structure for
WNK4
ECgene alternative splicing isoforms for
WNK4

Expression for WNK4 Gene

mRNA expression in normal human tissues for WNK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for WNK4 Gene

This gene is overexpressed in Colon - Transverse (9.4), Kidney - Cortex (8.9), Esophagus - Mucosa (6.2), and Prostate (5.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for WNK4 Gene

SOURCE GeneReport for Unigene cluster for WNK4 Gene Hs.105448

mRNA Expression by UniProt/SwissProt for WNK4 Gene

Q96J92-WNK4_HUMAN
Tissue specificity: Expressed in kidney, colon and skin.
genes like me logo Genes that share expressions with WNK4: view

Orthologs for WNK4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for WNK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia WNK4 36
  • 99.44 (n)
  • 99.36 (a)
WNK4 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia WNK4 36
  • 88.78 (n)
  • 88.73 (a)
WNK4 37
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia WNK4 36
  • 87.23 (n)
  • 87.31 (a)
WNK4 37
  • 60 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Wnk4 36
  • 85.31 (n)
  • 87.55 (a)
Wnk4 16
Wnk4 37
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia WNK4 37
  • 76 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia WNK4 37
  • 56 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Wnk4 36
  • 84.96 (n)
  • 87.14 (a)
chicken
(Gallus gallus)
Aves LOC777580 36
  • 70.94 (n)
  • 71.79 (a)
WNK4 37
  • 49 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia WNK4 37
  • 48 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii CABZ01069042.1 37
  • 31 (a)
OneToMany
CABZ01084815.1 37
  • 31 (a)
OneToMany
WNK4 (1 of 4) 37
  • 87 (a)
OneToMany
WNK4 (3 of 4) 37
  • 37 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Wnk 37
  • 14 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea wnk-1 37
  • 19 (a)
OneToMany
rice
(Oryza sativa)
Liliopsida Os11g0160300 36
  • 51.62 (n)
  • 48.51 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.28467 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 72 (a)
OneToMany
Species with no ortholog for WNK4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)

Evolution for WNK4 Gene

ENSEMBL:
Gene Tree for WNK4 (if available)
TreeFam:
Gene Tree for WNK4 (if available)

Paralogs for WNK4 Gene

Paralogs for WNK4 Gene

genes like me logo Genes that share paralogs with WNK4: view

Variants for WNK4 Gene

Sequence variations from dbSNP and Humsavar for WNK4 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs2290040 -- 42,795,422(-) GCAGA(A/G)TGGAG intron-variant
rs2290041 - 42,795,302(-) GCTAG(A/G)GAGGG reference, missense
rs2290042 -- 42,795,145(-) GGGCA(C/T)GGAGG synonymous-codon, reference
rs6503719 -- 42,789,145(+) TGGGC(A/G)AGAAA intron-variant
rs7224798 -- 42,781,328(+) CTGGG(A/C)GCCCC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for WNK4 Gene

Variant ID Type Subtype PubMed ID
esv33998 OTHER Inversion 15654335
nsv833450 CNV Loss 17160897
nsv908257 CNV Loss 21882294
nsv827998 CNV Loss 20364138

Relevant External Links for WNK4 Gene

HapMap Linkage Disequilibrium report
WNK4
Human Gene Mutation Database (HGMD)
WNK4

Disorders for WNK4 Gene

(1) OMIM Diseases for WNK4 Gene (601844)

UniProtKB/Swiss-Prot

WNK4_HUMAN
  • Pseudohypoaldosteronism 2B (PHA2B) [MIM:614491]: An autosomal dominant disorder characterized by hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. {ECO:0000269 PubMed:11498583}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(4) University of Copenhagen DISEASES for WNK4 Gene

(9) Novoseek inferred disease relationships for WNK4 Gene

Disease -log(P) Hits PubMed IDs
pseudohypoaldosteronism 96.5 22
gordon syndrome 95 6
hyperkalemia 87.2 18
hyperchloremia 77.6 1
genetic hypertension 68.3 2

Relevant External Links for WNK4

Genetic Association Database (GAD)
WNK4
Human Genome Epidemiology (HuGE) Navigator
WNK4
genes like me logo Genes that share disorders with WNK4: view

Publications for WNK4 Gene

  1. Genetic variants of WNK4 in whites and African Americans with hypertension. (PMID: 12719438) Erlich P.M. … DeStefano A.L. (Hypertension 2003) 3 23 49
  2. Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension. (PMID: 14616768) Benjafield A.V. … Morris B.J. (Clin. Genet. 2003) 3 23 49
  3. WNK4 intron 10 polymorphism is not associated with hypertension. (PMID: 14967840) Speirs H.J. … Morris B.J. (Hypertension 2004) 3 23 49
  4. The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. (PMID: 15824464) Matayoshi T. … Kawano Y. (Hypertens. Res. 2004) 3 23 49
  5. Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. (PMID: 15309683) Kokubo Y. … Miyata T. (J. Hum. Genet. 2004) 3 23 49

Products for WNK4 Gene

Sources for WNK4 Gene

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